dépistage néonatal

News and updates from the Public Health England screening programmes

AbstractObjective. To establish short- and long-term adverse outcome frequencies related to a late diagnosis of congenital adrenal hyperplasia (CAH) in the abs

The necessity of early treatment for lysosomal storage diseases (LSDs) has triggered the development of newborn screening for LSDs in recent years. Here we report the first 70,000 newborns screened for Mucopolysaccharidosis (MPS) type 4A (Morquio syndrome) and other LSDs by an 8-plex assay including the original 4-plex LSD screening tandem mass spectrometry (MS/MS) assay for Pompe disease, Fabry disease, Gaucher disease, and MPS I disease. The additional reaction for MPS II, MPS 3B, MPS 4A, and MPS 6 enzymes was performed separately from the 4-plex reaction. The two reactions were quenched and extracted, then combined before carrying out a single 2-min UPLC-MS/MS analysis. From Mar. 2018 to Apr. 2019, 73,743 newborns were screened with the 8-plex LSD screening assay. The 8-plex assay revealed a better analytical precision than the previous 4-plex assay possibly because the 8-plex was carried out using UPLC-MS/MS. Six newborns were found to have low MPS-4A enzyme (N-acetylgalactosamine-6-sulfatase) activity and biallelic GALNS pathogenic mutations in trans; these patients are presumably affected with MPS4A, making an incidence of one in 12,291 (95% confident interval (CI): 5633-26,817). One mutation, c.857C > T (p.T286 M) of the GALNS gene, accounted 5 of the 12 mutated alleles. These newborns had immature vertebral bodies at 1 month of age, and one case was treated with elosulfase alfa 2 mg/kg/week starting from 4 months of age. Among other MPSs screened, one case of MPS I, 3 cases of MPS II, and 3 cases of MPS 3B were detected. One case of mucolipidosis type III was also diagnosed. In conjunction with another 9 patients of Pompe disease, Gaucher disease, and classical Fabry disease, making an incidence of LSDs as one in 3206 newborns (95% CI: 2137 - 4811). The one with infantile-onset Pompe disease and the one with Gaucher disease were treated since the age of 8 days and 41 days respectively. Routine newborn screening of MPS 4A and other LSDs were made possible by the 8-plex LSD screening assay. However, detailed phenotype prediction and the time to start treatment will need further elucidation.

The first test to aid in screening newborns for Duchenne muscular dystrophy (DMD) has received FDA authorization for marketing.Authorization of the GSP Neonatal

Newborn screening (NBS) is a public health programme for early diagnosis of treatable, mostly genetic, diseases, such as inherited metabolic diseases (IEM). Early treatment in a latent disease stage can prevent disease manifestations, which for diseases on many NBS panels include irreversible brain and organ damage and death [1-3]. Internationally, NBS was started > 50 years ago and in Denmark for phenylketonuria (PKU) in 1975. NBS for PKU became the paradigm for a well-functioning, cost-effective screening.

Hemoglobin separation techniques are the most commonly used laboratory methods in newborn screening and confirmatory testing programs for hemoglobinopathies. However, such protein-based testing cannot accurately detect several hemoglobinopathies in newborns, especially when β-thalassemia mutations are involved. Here, we describe a consecutive cohort of newborns who were identified by newborn screening to have a likely diagnosis of sickle-β+-thalassemia (having an “FSA” pattern) who were determined to have sickle cell traits by confirmatory and genetic testing. We illustrate the clinical utility of genetic testing to make a correct and timely diagnosis in the setting of newborn screening for hemoglobinopathies.

AbstractA fast and reliable method for the determination of hemoglobinopathies and thalassemias by high-resolution accurate mass spectrometry (HRAM/MS) is presented. The established method was verified in a prospective clinical study (HRAM/MS vs. high-pressure liquid chromatography [HPLC]) of 5335 de-identified newborn samples from the Hamburg area. The analytical method is based on a dual strategy using intact protein ratios for thalassemias and tryptic digest fragments for the diagnosis of hemoglobinopathies. Due to the minimal sample preparation and the use of flow injection, the assay can be considered as a high-throughput screening approach for newborn screening programs (2 min/sample). Using a simple dried blood spot (DBS) extraction (tryptic digest buffer), the following results were obtained: (1) a carrier incidence of 1:100 newborns (35 FAS, nine FAC, eight FAD and two FAE), and (2) no homozygous affected patient was detected. Using the HRAM/MS protocol, an unknown Hb mutation was identified and confirmed by genetic testing. In addition to greater specificity toward rare mutations and β-thalassemia, the low price/sample (1–2€) as well as an automated data processing represent the major benefits of the described HRAM/MS method.

Adrenoleukodystrophy (ALD) is a rare X‐linked disease caused by a mutation of the peroxisomal ABCD1 gene. This review summarizes our current understanding of the pathogenic cell‐ and tissue‐specifi